Mesenchymal stem cells (MSCs) are a population of cells found in connective tissues, including skeletal muscle dermis. MSCs have 1) an apparent unlimited growth potential and 2) the ability to differentiate, when stimulated, into a number of mesodermally-derived tissues, including cartilage and bone. Once isolated and grown in culture, andy required number of autologous MSCs can be obtained and then grown into biocompatible, biodgradable polymer mesh for use in tissue regeneration. The proposed research will investigate the use of mesenchymal stem cells for the treatment of full-thickness cartilage defects that model osteoarthritis. The objective of this project is to define the effects of autologous MSCs on healing of cartilage defects and to quantify the architectural and mechanical properties of the regenerated articular surface. For the experimental work full thickness defects will be created in the articular cartilage of adult male rabbits on both non- weight bearing and weight bearing surfaces. There will be unoperated controls and six experimental groups: untreated defects, defects with polymer alone, polymer plus MSCs cultured in the polymer for two weeks in vitro (standard protocol), polymer plus MSCs cultured in the polymer for 24 hours, polymer plus MSCs in the polymer for 24 hours, polymer plus MSCs cultured in the polymer for 2 weeks but killed by freeze-thaw just prior to implantation, and polymer plus smooth muscle cells cultured in vitro for 2 weeks. The last two groups will serve as controls for the specificity of live MSCs to regenerate cartilage and bone. Tissues will be harvested at 6, 12 and 24 weeks post-implantation and assayed for histological appearance and biomechanical properties. This will be a preclinical trial prior to the use of MSCs to regenerate articular cartilage in humans. PROPOSED COMMERCIAL APPLICATION This research could provide a revolutionary approach to cartilage repair due to osteoarthritis, infectious arthritis,and sports injury. It offers repair of joints needing either cartilage or bone, or both, treatment of any sized defect in any joint, and treatment of multiple joints in the same individual. The ability of MSCs to regenerate cartilage can then be extended to meniscus and vertebral disc.